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1
Eriksson, A. J., B. C. le Roux, H. J. Geldenhuys y D. V. Meal. "Study of airgap breakdown characteristics under ambient conditions of reduced air density". IEE Proceedings A Physical Science, Measurement and Instrumentation, Management and Education, Reviews 133, n.º 8 (1986): 485. http://dx.doi.org/10.1049/ip-a-1.1986.0067.
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Al-Qarni, Ali y Ayman EL-Refaie. "Magnetic Gears and Magnetically Geared Machines with Reduced Rare-Earth Elements for Vehicle Applications". World Electric Vehicle Journal 12, n.º 2 (24 de marzo de 2021): 52. http://dx.doi.org/10.3390/wevj12020052.
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This paper covers a new emerging class of electrical machines, namely, Magnetic Gears (MGs) and Magnetically Geared Machines (MGMs). This particular kind of gears/machines is capable of either scaling up or down the revolutions-per-minute to meet various load profiles as in the case of mechanical gearboxes, but with physical isolation between the rotating components. This physical isolation between the rotational components leads to several advantages in favor of MGs and MGMs over mechanical gearboxes. Although MGs and MGMs can potentially provide a solution for some of the practical issues of mechanical gears, MGs and MGMs have two major challenges that researchers have been trying to address. Those challenges are the high usage of rare-earth Permanent Magnet (PM) materials and the relatively complex mechanical structure of MGs and MGMs, both of which are a consequence of the multi-airgap design. This paper presents designs that reduce the PM rare-earth content for Electric Vehicles (EVs). Additionally, the paper will ensure having practical designs that do not run the risk of permanent demagnetization. The paper will also discuss some new designs to simplify the mechanical structure.
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Liu, Yan, Wenliang Zhao, Xue Fan, Xiuhe Wang y Byung-il Kwon. "Optimal design of a surface-mounted permanent magnet motor with multi-grade ferrite magnets to reduce torque pulsations". International Journal of Applied Electromagnetics and Mechanics 64, n.º 1-4 (10 de diciembre de 2020): 79–89. http://dx.doi.org/10.3233/jae-209310.
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This paper proposes an optimal design for a surface-mounted permanent magnet motor (SPMM) to reduce torque pulsations, including cogging torque and torque ripple, by using multi-grade ferrite magnets. Based on a conventional SPMM with single-grade ferrite magnets, the proposed SPMM is designed with four-grade ferrite magnets and then optimized to minimize torque pulsations by maintaining the required torque, utilizing the Kriging method and a genetic algorithm. The results obtained by the finite element analysis show that the optimized SPMM with multi-grade ferrite magnets exhibits improved airgap flux density distribution with highly reduced cogging torque and torque ripple by maintaining the same average torque, as compared to the conventional SPMM. Furthermore, the analysis of the working points for the multi-grade ferrite magnets reveals that the optimized SPMM has good durability against the irreversible demagnetization.
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Ouakad, Hassen M., Nouha Alcheikh y Mohammad I. Younis. "Static and Dynamic Analysis of Electrostatically Actuated MEMS Shallow Arches for Various Air-Gap Configurations". Micromachines 12, n.º 8 (5 de agosto de 2021): 930. http://dx.doi.org/10.3390/mi12080930.
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In this research, we investigate the structural behavior, including the snap-through and pull-in instabilities, of in-plane microelectromechanical COSINE-shaped and electrically actuated clamped-clamped micro-beams resonators. The work examines various electrostatic actuation patterns including uniform and non-uniform parallel-plates airgap arrangements, which offer options to actuate the arches in the opposite and same direction of their curvature. The nonlinear equation of motion of a shallow arch is discretized into a reduced-order model based on the Galerkin’s expansion method, which is then numerically solved. Static responses are examined for various DC electrostatic loads starting from small values to large values near pull-in and snap-through instability ranges, if any. The eigenvalue problem of the micro-beam is solved revealing the variations of the first four natural frequencies as varying the DC load. Various simulations are carried out for several case studies of shallow arches of various geometrical parameters and airgap arrangements, which demonstrate rich and diverse static and dynamic behaviors. Results show few cases with multi-states and hysteresis behaviors where some with only the pull-in instability and others with both snap-through buckling and pull-in instabilities. It is found that the micro-arches behaviors are very sensitive to the electrode’s configuration. The studied configurations reveal different possibilities to control the pull-in and snap-through instabilities, which can be used for improving arches static stroke range as actuators and for realizing wide-range tunable micro-resonators.
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Wang, K., Z. Q. Zhu y Robert Nilssen. "Using Third Harmonic for Shape Optimization of Flux Density Distribution in Linear Permanent-Magnet Machine". Applied Mechanics and Materials 416-417 (septiembre de 2013): 359–65. http://dx.doi.org/10.4028/www.scientific.net/amm.416-417.359.
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This paper presents a sinusoidal permanent magnet (PM) shaping technique with third harmonic to improve the electromagnetic thrust force in linear slotless PM machines without sacrificing the thrust force ripple. Slotless PM linear machine possesses relatively low thrust force ripple due to the absence of cogging force, compared with slotted topology. However, thrust force ripple of the machine with rectangular PM shape still exists due to nonsinusoidal airgap flux density distribution produced by PMs. Sinusoidal shaping techniques can be used to reduce the thrust force ripple but the average thrust force is reduced as well. Therefore, a simple PM shaping technique with optimal 3rd harmonic is presented to improve the output thrust force but not to increase the thrust force ripple. The sinusoidal plus 3rd harmonic shaping technique is analytically demonstrated together conventional sinusoidal shaping method and verified with finite element method. The results show that the electromagnetic performance can be significantly improved.
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Ou, Hu, Mao y Li. "A Method for Reducing Cogging Torque of Integrated Propulsion Motor". Journal of Marine Science and Engineering 7, n.º 7 (21 de julio de 2019): 236. http://dx.doi.org/10.3390/jmse7070236.
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How to reduce the cogging torque of the integrated propeller motor is an important means to improve its noise performance because cogging torque is one of the key factors causing torque ripple. We proposed a method to reduce the cogging torque by optimizing the size of the Halbach array’s auxiliary pole. First, an analytical model for the airgap magnetic field of Halbach array based on different dimensions (including the circumference ratio and the radial thickness) of the auxiliary pole is given. Then the finite element method is used to verify the analytical model. On the basis, we calculated the cogging torque of different size of auxiliary poles as sample data by combining different circumference ratio and radial thickness. Furthermore, using the two-variable single-objective neural network genetic optimization algorithm based on Backpropagation (BP), we obtain the optimal size of the auxiliary pole. Finally, comparing the motor cogging torque and torque ripple before and after optimization indicated that the cogging torque and torque ripple are effectively reduced after optimizing the size of the auxiliary pole.
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Kim, Kwangsoo. "A Study on Stator Design for Electromagnetic Noise Reduction in Washing Machine Motor". Turkish Journal of Computer and Mathematics Education (TURCOMAT) 12, n.º 6 (11 de abril de 2021): 585–89. http://dx.doi.org/10.17762/turcomat.v12i6.1999.
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Received:11 november 2020; Accepted: 27 December 2020; Published online: 05 April 2021
Abstract : For low cost, spoke type ferrite magnet motors with small air gap are using to washing machine. At that time, a noise problem occurs, so a design to reduce the noise is required. In the washing machine, set noise increased due to the reduction of air gap of motor at high speed spin mode. Not only the overall noise, but also the harmonics noises are greatly increased at set. As a result of set noise test and noise analysis through finite elements method, a stator tooth shoe shape in which the magnetic flux changes rapidly is cause of noise. Its shape creates many harmonics of load torque. The harmonics component of the load torque increases the overall noise of the set. The harmonics noise of the set has a large correlation with radial force component as well as the torque ripple. Especially, it is found that the harmonics noise of the set is related to harmonics component of load torque and the harmonics component of the radial force at stator tooth. The noise is reduced by applying the new design of stator tooth shoe that can minimize the change in magnetic flux through the noise cause analysis. Through this research, the harmonics noise as well as overall noise are reduced at small airgap motor. Therefore, it is possible to develop cost reduction motor for washing machine.
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Faßbender, Heike y Julius Mayer. "A revised moment error expression for the AIRGA algorithm". Analele Universitatii "Ovidius" Constanta - Seria Matematica 26, n.º 2 (1 de julio de 2018): 87–104. http://dx.doi.org/10.2478/auom-2018-0020.
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Abstract The fully adaptive rational global Arnoldi method (AIRGA) for the modelorder reduction of second-order multi-input multi-output systems with proportional damping is revisited. The method automatically generates a reduced system approximating the transfer function. It is based on a moment-matching approach. The expansion points are determined iteratively. The reduced order and the number of moments matched per expansion point are determined adaptively using a heuristic based on an error estimation. A revised moment error expression is presented as well as some related findings.
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Shin, Hye-Won, David A. Shelley, Edward M. Henderson, Anne Fitzpatrick, Benjamin Gaston y Steven C. George. "Airway nitric oxide release is reduced after PBS inhalation in asthma". Journal of Applied Physiology 102, n.º 3 (marzo de 2007): 1028–33. http://dx.doi.org/10.1152/japplphysiol.01012.2006.
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Exhaled nitric oxide (NO) is elevated in asthma, but the underlying mechanisms remain poorly understood. Recent results in subjects with asthma have reported a decrease in exhaled breath pH and ammonia, as well as altered expression and activity of glutaminase in both alveolar and airway epithelial cells. This suggests that pH-dependent nitrite conversion to NO may be a source of exhaled NO in the asthmatic airway epithelium. However, the anatomic location (i.e., airway or alveolar region) of this pH-dependent NO release has not been investigated and could impact potential therapeutic strategies. We quantified airway (proximal) and alveolar (peripheral) contributions to exhaled NO at baseline and then after PBS inhalation in stable (mild-intermittent to severe) asthmatic subjects (20–44 yr old; n = 9) and healthy controls (22–41 yr old; n = 6). The mean (SD) maximum airway wall flux (pl/s) and alveolar concentration (ppb) at baseline in asthma subjects and healthy controls was 2,530 (2,572) and 5.42 (7.31) and 1,703 (1,567) and 1.88 (1.29), respectively. Compared with baseline, there is a significant decrease in the airway wall flux of NO in asthma as early as 15 min and continuing for up to 60 min (maximum −28% at 45 min) after PBS inhalation without alteration of alveolar concentration. Healthy control subjects did not display any changes in exhaled NO. We conclude that elevated airway NO at baseline in asthma is reduced by inhaled PBS. Thus airway NO may be, in part, due to nitrite conversion to NO and is consistent with airway pH dysregulation in asthma.
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Lim, Dae Hyun, Jae Youn Cho, Marina Miller, Kirsti McElwain, Shauna McElwain y David H. Broide. "Reduced peribronchial fibrosis in allergen-challenged MMP-9-deficient mice". American Journal of Physiology-Lung Cellular and Molecular Physiology 291, n.º 2 (agosto de 2006): L265—L271. http://dx.doi.org/10.1152/ajplung.00305.2005.
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Matrix metalloproteinases (MMPs) are a family of extracellular proteases that are responsible for the degradation of the extracellular matrix during tissue remodeling. We have used a mouse model of allergen-induced airway remodeling to determine whether MMP-9 plays a role in airway remodeling. MMP-9-deficient and wild-type (WT) mice were repetitively challenged intranasally with ovalbumin (OVA) antigen to develop features of airway remodeling including peribronchial fibrosis and increased thickness of the peribronchial smooth muscle layer. OVA-challenged MMP-9-deficient mice had less peribronchial fibrosis and total lung collagen compared with OVA-challenged WT mice. There was no reduction in mucus expression, smooth muscle thickness, or airway responsiveness in OVA-challenged MMP-9-deficient compared with OVA-challenged WT mice. OVA-challenged MMP-9-deficient mice had reduced levels of bronchoalveolar lavage (BAL) regulated on activation, normal T cell expressed, and secreted (RANTES), as well as reduced numbers of BAL and peribronchial eosinophils compared with OVA-challenged WT mice. There were no significant difference in levels of BAL eotaxin, thymus- and activation-regulated chemokine (TARC), or macrophage-derived chemokine (MDC) in OVA-challenged WT compared with MMP-9-deficient mice. Overall, this study demonstrates that MMP-9 may play a role in mediating selected aspects of allergen-induced airway remodeling (i.e., modest reduction in levels of peribronchial fibrosis) but does not play a significant role in mucus expression, smooth muscle thickness, or airway responsiveness.
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Zimmermann, Richard E. "Vent Control as a Means of Enhancing Airbag Performance". Shock and Vibration 9, n.º 3 (2002): 123–28. http://dx.doi.org/10.1155/2002/158642.
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Typical automotive airbag systems have a fixed area vent for exiting gasses. The US Army Cockpit Airbag System (CABS) is unvented to prolong the period during which the system can provide occupant protection during extended helicopter crash scenarios. In each application, system performance may be enhanced by providing a controlled vent area. This paper describes work conducted under a Phase I SBIR program sponsored by the NASA Langley Research Center. The work was focused on eventual inflatable restraint system applications in general aviation aircraft, and showed that appropriate vent control offers many enhancements. Two series of tests conducted during Phase I showed that inflatable restraint system size and weight can be reduced without degrading performance, injury potential in an out of position situation (OOPS) deployment can be reduced, and peak bag pressures can be reduced (at any temperature) during normal operation.
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Abdala-Valencia, Hiam, Sergejs Berdnikovs, Christine A. McCary, Daniela Urick, Riti Mahadevia, Michelle E. Marchese, Kelsey Swartz, Lakiea Wright, Gökhan M. Mutlu y Joan M. Cook-Mills. "Inhibition of allergic inflammation by supplementation with 5-hydroxytryptophan". American Journal of Physiology-Lung Cellular and Molecular Physiology 303, n.º 8 (15 de octubre de 2012): L642—L660. http://dx.doi.org/10.1152/ajplung.00406.2011.
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Clinical reports indicate that patients with allergy/asthma commonly have associated symptoms of anxiety/depression. Anxiety/depression can be reduced by 5-hydroxytryptophan (5-HTP) supplementation. However, it is not known whether 5-HTP reduces allergic inflammation. Therefore, we determined whether 5-HTP supplementation reduces allergic inflammation. We also determined whether 5-HTP decreases passage of leukocytes through the endothelial barrier by regulating endothelial cell function. For these studies, C57BL/6 mice were supplemented with 5-HTP, treated with ovalbumin fraction V (OVA), house dust mite (HDM) extract, or IL-4, and examined for allergic lung inflammation and OVA-induced airway responsiveness. To determine whether 5-HTP reduces leukocyte or eosinophil transendothelial migration, endothelial cells were pretreated with 5-HTP, washed and then used in an in vitro transendothelial migration assay under laminar flow. Interestingly, 5-HTP reduced allergic lung inflammation by 70–90% and reduced antigen-induced airway responsiveness without affecting body weight, blood eosinophils, cytokines, or chemokines. 5-HTP reduced allergen-induced transglutaminase 2 (TG2) expression and serotonylation (serotonin conjugation to proteins) in lung endothelial cells. Consistent with the regulation of endothelial serotonylation in vivo, in vitro pretreatment of endothelial cells with 5-HTP reduced TNF-α-induced endothelial cell serotonylation and reduced leukocyte transendothelial migration. Furthermore, eosinophil and leukocyte transendothelial migration was reduced by inhibitors of transglutaminase and by inhibition of endothelial cell serotonin synthesis, suggesting that endothelial cell serotonylation is key for leukocyte transendothelial migration. In summary, 5-HTP supplementation inhibits endothelial serotonylation, leukocyte recruitment, and allergic inflammation. These data identify novel potential targets for intervention in allergy/asthma.
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Papapetropoulos, Andreas, Davina C. M. Simoes, Georgia Xanthou, Charis Roussos y Christina Gratziou. "Soluble guanylyl cyclase expression is reduced in allergic asthma". American Journal of Physiology-Lung Cellular and Molecular Physiology 290, n.º 1 (enero de 2006): L179—L184. http://dx.doi.org/10.1152/ajplung.00330.2005.
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Soluble guanylyl cyclase (sGC) is an enzyme highly expressed in the lung that generates cGMP contributing to airway smooth muscle relaxation. To determine whether the bronchoconstriction observed in asthma is accompanied by changes in sGC expression, we used a well-established murine model of allergic asthma. Histological and biochemical analyses confirmed the presence of inflammation in the lungs of mice sensitized and challenged with ovalbumin (OVA). Moreover, mice sensitized and challenged with OVA exhibited airway hyperreactivity to methacholine inhalation. Steady-state mRNA levels for all sGC subunits (α1, α2, and β1) were reduced in the lungs of mice with allergic asthma by 60–80%, as estimated by real-time PCR. These changes in mRNA were paralleled by changes at the protein level: α1, α2, and β1 expression was reduced by 50–80% as determined by Western blotting. Reduced α1 and β1 expression in bronchial smooth muscle cells was demonstrated by immunohistochemistry. To study if sGC inhibition mimics the airway hyperreactivity seen in asthma, we treated naïve mice with a selective sGC inhibitor. Indeed, in mice receiving ODQ the methacholine dose response was shifted to the left. We conclude that sGC expression is reduced in experimental asthma contributing to the observed airway hyperreactivity.
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Xue, Z., Y. Yu, H. Gao, S. J. Gunst y R. S. Tepper. "Chronic continuous positive airway pressure (CPAP) reduces airway reactivity in vivo in an allergen-induced rabbit model of asthma". Journal of Applied Physiology 111, n.º 2 (agosto de 2011): 353–57. http://dx.doi.org/10.1152/japplphysiol.01345.2010.
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Previous studies have demonstrated that chronic mechanical strain produced by continuous positive airway pressure (CPAP) reduces in vivo airway reactivity in rabbits and ferrets. For CPAP to potentially have a therapeutic benefit for asthmatic subjects, the reduction in airway responsiveness would need to persist for 12–24 h after its discontinuation, require application for only part of the day, and be effective in the presence of atopic airway inflammation. In the present study, airway responsiveness to acetylcholine or methacholine was measured during mechanical ventilation following three different protocols in which active, nonanesthetized, tracheotomized rabbits were treated with High vs. Low CPAP (6 vs. 0 cmH2O). 1) High CPAP was applied continuously for 4 days followed by 1 day of Low CPAP; 2) High CPAP was applied at night and Low CPAP during the daytime for 4 days, and 3) High CPAP was applied for 4 days in animals following ovalbumin (Ova) sensitization and challenge. For all three protocols, treatment with High CPAP resulted in significantly reduced airway responsiveness compared with treatment with Low CPAP. Cumulatively, our in vivo results in rabbits suggest that high CPAP, even when applied only at night, produces a persistent reduction of airway responsiveness. In addition, CPAP reduces airway responsiveness even in the presence of atopic airway inflammation.
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Guedes, Alonso G. P., Jaime Paulin, Laura Rivero-Nava, Hirohito Kita, Frances E. Lund y Mathur S. Kannan. "CD38-deficient mice have reduced airway hyperresponsiveness following IL-13 challenge". American Journal of Physiology-Lung Cellular and Molecular Physiology 291, n.º 6 (diciembre de 2006): L1286—L1293. http://dx.doi.org/10.1152/ajplung.00187.2006.
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The transmembrane glycoprotein CD38 in airway smooth muscle is the source of cyclic-ADP ribose, an intracellular calcium-releasing molecule, and is subject to regulatory effects of cytokines such as interleukin (IL)-13, a cytokine implicated in asthma. We investigated the role of CD38 in airway hyperresponsiveness using a mouse model of IL-13-induced airway disease. Wild-type (WT) and CD38-deficient (CD38KO) mice were intranasally challenged with 5 μg of IL-13 three times on alternate days under isoflurane anesthesia. Lung resistance (RL) in response to inhaled methacholine was measured 24 h after the last challenge in pentobarbital-anesthetized, tracheostomized, and mechanically ventilated mice. Bronchoalveolar cytokines, bronchoalveolar and parenchymal inflammation, and smooth muscle contractility and relaxation using tracheal segments were also evaluated. Changes in methacholine-induced RL were significantly greater in the WT than in the CD38KO mice following intranasal IL-13 challenges. Airway reactivity after IL-13 exposure, as measured by the slope of the methacholine dose-response curve, was significantly higher in the WT than in the CD38KO mice. The rate of isometric force generation in tracheal segments (e.g., smooth muscle reactivity) was greater in the WT than in the CD38KO mice following incubation with IL-13. IL-13 treatment reduced isoproterenol-induced relaxations to similar magnitudes in tracheal segments obtained from WT and CD38KO mice. Both WT and CD38KO mice developed significant bronchoalveolar and parenchymal inflammation after IL-13 challenges compared with naïve controls. The results indicate that CD38 contributes to airway hyperresponsiveness in lungs exposed to IL-13 at least partly by increasing airway smooth muscle reactivity to contractile agonists.
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O’Donovan, Siobhan, Corinna van den Heuvel, Matthew Baldock y Roger W. Byard. "Injuries, death and vehicle airbag deployment". Medicine, Science and the Law 60, n.º 2 (22 de enero de 2020): 147–49. http://dx.doi.org/10.1177/0025802419892392.
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Airbags are impact-activated safety devices which deploy from the interior of vehicles to protect occupants from trauma during crashes. Although airbags effectively reduce the risk of death and injury, this it is not without issues. For example, high-impact unbelted rigid-barrier testing in the USA led to the adoption of powerful, large airbags that were associated with numerous airbag-related deaths and injuries. In contrast, European designs were tested and certified in conjunction with the use of three-point restraint systems, meaning that the airbags could be smaller with reduced ‘punch-out’ power. An overview is provided of the mechanism of action of airbags and the associated non-lethal and lethal injuries that may be sustained by vehicle occupants.
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Shirzadi, Hooman, Hassan Zohoor y Sadegh Naserkhaki. "Biomechanical simulation of eye-airbag impacts during vehicle accidents". Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine 232, n.º 7 (10 de junio de 2018): 699–707. http://dx.doi.org/10.1177/0954411918778063.
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Airbags are safety devices in vehicles effectively suppressing passengers’ injuries during accidents. Although there are still many cases of eye injuries reported due to eye-airbag impacts in recent years. Biomechanical approaches are now feasible and can considerably help experts to investigate the issue without ethical concerns. The eye-airbag impact–induced stresses/strains in various components of the eye were found to investigate the risk of injury in different conditions (impact velocity and airbag pressure). Three-dimensional geometry of the eyeball, fat and bony socket as well as the airbag were developed and meshed to develop a finite element model. Nonlinear material properties of the vitreous body and sclera were found through the in vitro tests on ovine samples and for the other components were taken from the literature. The eye collided the airbag due to the velocity field in the dynamic explicit step in Abaqus. Results of compression tests showed a nonlinear curve for vitreous body with average ultimate stress of 22 (18–25) kPa. Tensile behavior of sclera was viscoelastic nonlinear with ultimate stresses changing from 2.51 (2.3–2.7) to 4.3 (4–4.6) MPa when loading strain rate increased from 10 to 600 mm/min. Sclera, ciliary body, cornea and lens were the eye components with highest stresses (maximum stress reached up to 9.3 MPa). Cornea, retina and choroid experienced the highest strains with the maximum up to 14.1%. According to the previously reported injury criteria for cornea, it was at high risk of injury considering both stress and strains. Reduced pressure of the airbag was beneficial decreased stress of all components. Comprehensive investigations in this area can disclose biomechanical behavior of the eye during eye-airbag impact. Effective guidelines can be drawn for airbag design for instance the airbag pressure which reduces risk of eye injury.
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Kobayashi, Yoshiki, Akira Kanda, Yasutaka Yun, Dan Van Bui, Kensuke Suzuki, Shunsuke Sawada, Mikiya Asako y Hiroshi Iwai. "Reduced Local Response to Corticosteroids in Eosinophilic Chronic Rhinosinusitis with Asthma". Biomolecules 10, n.º 2 (18 de febrero de 2020): 326. http://dx.doi.org/10.3390/biom10020326.
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Eosinophilic chronic rhinosinusitis (ECRS), a subgroup of chronic rhinosinusitis with nasal polyps, is recognized as a refractory eosinophilic disorder characterized by both upper and lower airway inflammation. In some severe cases, disease control is poor, likely due to local steroid insensitivity. In this study, we focused on protein phosphatase 2A (PP2A), a key factor regulating glucocorticoid receptor (GR) nuclear translocation, and examined its association with local responses to corticosteroids in eosinophilic airway inflammation. Our results indicated reduced responses to corticosteroids in nasal epithelial cells from ECRS patients with asthma, which were also associated with decreased PP2A mRNA expression. Eosinophil peroxidase stimulates elevated PP2A phosphorylation levels, reducing PP2A protein expression and activity. In addition, mRNA levels of inflammatory mediators (TSLP, IL-25, IL-33, CCL4, CCL5, CCL11, and CCL26) associated with eosinophilic airway inflammation in epithelial cells were increased in nasal polyps (eosinophil-rich areas) compared with those in uncinate process tissues (eosinophil-poor areas) from the same patients. PP2A reduction by siRNA reduced GR nuclear translocation, whereas PP2A overexpression by plasmid transfection, or PP2A activation by formoterol, enhanced GR nuclear translocation. Collectively, our findings indicate that PP2A may represent a promising therapeutic target in refractory eosinophilic airway inflammation characterized by local steroid insensitivity.
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Fogel, Robert B., Atul Malhotra, Steven A. Shea, Jill K. Edwards y David P. White. "Reduced genioglossal activity with upper airway anesthesia in awake patients with OSA". Journal of Applied Physiology 88, n.º 4 (1 de abril de 2000): 1346–54. http://dx.doi.org/10.1152/jappl.2000.88.4.1346.
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We examined whether topical upper airway anesthesia leads to a reduction in genioglossal (GG) electromyogram (EMG) in patients with obstructive sleep apnea (OSA). Airway mechanics were also evaluated. In 13 patients with OSA, we monitored GG EMG during tidal breathing and during the application of pulses of negative airway pressure (−10 to −12 cmH2O). Airflow resistance and airway collapsibility were determined. All measurements were performed with and without topical anesthesia (lidocaine). Anesthesia led to a significant fall in the peak GG EMG response to negative pressure from 36.1 ± 4.7 to 24.8 ± 5.3% (SE) of maximum ( P < 0.01). This was associated with a fall in phasic and tonic EMG during tidal breathing (phasic from 24.4 ± 4.1 to 16.4 ± 3.4% of maximum and tonic from 10.9 ± 1.6 to 8.0 ± 1.3% of maximum, P < 0.01). A significant rise in pharyngeal airflow resistance was also observed. Our results demonstrate that topical receptor mechanisms in the nasopharynx importantly influence dilator muscle activity and are likely important in driving the augmented dilator muscle activity seen in the apnea patient.
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Taranto-Montemurro, Luigi, Scott A. Sands, Bradley A. Edwards, Ali Azarbarzin, Melania Marques, Camila de Melo, Danny J. Eckert, David P. White y Andrew Wellman. "Desipramine improves upper airway collapsibility and reduces OSA severity in patients with minimal muscle compensation". European Respiratory Journal 48, n.º 5 (6 de octubre de 2016): 1340–50. http://dx.doi.org/10.1183/13993003.00823-2016.
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We recently demonstrated that desipramine reduces the sleep-related loss of upper airway dilator muscle activity and reduces pharyngeal collapsibility in healthy humans without obstructive sleep apnoea (OSA). The aim of the present physiological study was to determine the effects of desipramine on upper airway collapsibility and apnoea–hypopnea index (AHI) in OSA patients.A placebo-controlled, double-blind, randomised crossover trial in 14 OSA patients was performed. Participants received treatment or placebo in randomised order before sleep. Pharyngeal collapsibility (critical collapsing pressure of the upper airway (Pcrit)) and ventilation under both passive (V′0,passive) and active (V′0,active) upper airway muscle conditions were evaluated with continuous positive airway pressure (CPAP) manipulation. AHI was quantified off CPAP.Desipramine reduced activePcrit(median (interquartile range) −5.2 (4.3) cmH2O on desipramineversus−1.9 (2.7) cmH2O on placebo; p=0.049) but not passivePcrit(−2.2 (3.4)versus−0.7 (2.1) cmH2O; p=0.135). A greater reduction in AHI occurred in those with minimal muscle compensation (defined asV′0,active−V′0,passive) on placebo (r=0.71, p=0.009). The reduction in AHI was driven by the improvement in muscle compensation (r=0.72, p=0.009).In OSA patients, noradrenergic stimulation with desipramine improves pharyngeal collapsibility and may be an effective treatment in patients with minimal upper airway muscle compensation.
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Hwang, Kun y Joo Ho Kim. "Need for Airbag and Seatbelt to Reduce Orbital Injuries From Steering Wheel Knob". Journal of Craniofacial Surgery 25, n.º 6 (noviembre de 2014): e590-e592. http://dx.doi.org/10.1097/scs.0000000000001078.
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Shore, S. A., R. A. Johnston, I. N. Schwartzman, D. Chism y G. G. Krishna Murthy. "Ozone-induced airway hyperresponsiveness is reduced in immature mice". Journal of Applied Physiology 92, n.º 3 (1 de marzo de 2002): 1019–28. http://dx.doi.org/10.1152/japplphysiol.00381.2001.
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During ozone (O3) exposure, adult mice decrease their minute ventilation (V˙e). To determine whether there are age-related differences in the ventilatory response to O3, A/J mice, aged 2, 4, 8, or 12 wk, were exposed to O3(0.3–3.0 parts/million for 3 h) in nose-only exposure plethysmographs. Baseline V˙e normalized for body weight (V˙e/g) decreased with increasing age, consistent with the higher metabolic rates of younger animals. O3 caused a concentration-related decrease inV˙e in mice of all ages, but the response was significantly less in 2-wk-old than in older mice. The increased baseline V˙e/g and smaller decrements inV˙e induced by O3 in immature mice resulted in an inhaled dose of O3 normalized for body weight that was three to four times higher than in adult mice. O3 exposure caused a dose-related increase in airway responsiveness in 8- and 12-wk-old mice but did not cause airway hyperresponsiveness at any dose in either 2- or 4-wk-old mice, although higher inhaled doses of O3 normalized for body weight were delivered to these younger animals. Interleukin-6 and macrophage inflammatory protein-2 levels in bronchoalveolar lavage fluid were also increased in 8-wk-old compared with 2-wk-old mice exposed to O3. The results suggest that immature mice are less sensitive than adult mice to O3, at least in terms of the ability of O3 to induce airway hyperresponsiveness and promote release of certain cytokines.
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Lim, Dae Hyun, Jae Youn Cho, Dae Jin Song, Sang Yeub Lee, Marina Miller y David H. Broide. "PI3Kγ-deficient mice have reduced levels of allergen-induced eosinophilic inflammation and airway remodeling". American Journal of Physiology-Lung Cellular and Molecular Physiology 296, n.º 2 (febrero de 2009): L210—L219. http://dx.doi.org/10.1152/ajplung.90275.2008.
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In this study, we have examined the role of phosphoinositide 3 kinase γ (PI3Kγ), a class Ib PI3K, in contributing to airway remodeling utilizing PI3Kγ-deficient mice exposed to chronic allergen challenge. Wild-type (WT) mice sensitized to ovalbumin (OVA) and chronically challenged with OVA for 1 mo developed significantly increased levels of eosinophilic inflammation and airway remodeling. In contrast, PI3Kγ-deficient mice challenged with OVA had significantly reduced numbers of bronchoalveolar lavage and peribronchial eosinophils compared with WT mice. There was no significant difference in the number of bone marrow or circulating peripheral blood eosinophils when comparing WT mice and PI3Kγ-deficient mice, suggesting that trafficking of eosinophils into the lung was reduced in PI3Kγ-deficient mice. PI3Kγ-deficient and WT mice had similar levels of IL-5 and eotaxin-1. The reduced eosinophil recruitment to the airway in PI3Kγ-deficient mice challenged with OVA was associated with significantly reduced numbers of TGF-β1+ peribronchial cells, reduced numbers of pSmad 2/3+ airway epithelial cells, and pSmad 2/3+ peribronchial cells, as well as significantly reduced levels of peribronchial fibrosis (quantitated by trichrome staining and image analysis as well as by lung collagen levels). In addition, the area of peribronchial α-smooth muscle staining was significantly reduced in PI3Kγ-deficient compared with WT mice. Overall, this study demonstrates an important role for PI3Kγ in mediating allergen-induced eosinophilic airway inflammation and airway remodeling, suggesting that PI3Kγ may be a novel therapeutic target in asthma.
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Thulesius, H. L., A. Cervin y M. Jessen. "Treatment with a topical glucocorticoid, budesonide, reduced the variability of rhinomanometric nasal airway resistance". Rhinology journal 52, n.º 1 (1 de marzo de 2014): 19–24. http://dx.doi.org/10.4193/rhino12.180.
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Background: Previous rhinomanometry studies have shown significant long-term variability of the nasal airway resistance and questioned the clinical validity of rhinomanometry. Research question: Could treatment with a topical glucocorticoid, budesonide, influence the long-term variability of active anterior rhinomanometry? Methods: Eight healthy volunteers participated in an unblinded controlled trial without, and later with, nasal budesonide once a day for 5 months. Their nasal airway resistance was measured every two weeks with active anterior rhinomanometry before and after decongestion with xylometazoline hydrochloride. In addition, subjective nasal obstruction was evaluated on a Visual Analogue Scale before each measurement. The participants had a year earlier been investigated with rhinomanometry every two weeks during 5 months but without budesonide treatment. We compared the variability of nasal airway resistance during the two periods with and without treatment with topical budesonide. Results: Budesonide significantly reduced mean nasal airway resistance and the standard deviation of the mean after decongestion for 6 of 8 participants. The mean reduction of the nasal airway resistance was 40% for the decongested nasal cavity compared to the period without treatment with nasal budesonide. Subjective nasal obstruction assessed by Visual Analogue Scale was reduced in 3 of the 8 participants. Conclusion: The variability of nasal airway resistance was significantly reduced by treatment with topical budesonide for 6 out of 8 healthy volunteers participating in an unblinded repeated 5 month trial where the participants served as their own controls.
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Quinn, Timothy J., Somer Taylor, Christine L. Wohlford-Lenane y David A. Schwartz. "IL-10 reduces grain dust-induced airway inflammation and airway hyperreactivity". Journal of Applied Physiology 88, n.º 1 (1 de enero de 2000): 173–79. http://dx.doi.org/10.1152/jappl.2000.88.1.173.
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To determine whether interleukin-10 (IL-10) could alter the development of grain dust-induced airway disease, we pretreated mice with either saline or IL-10 intravenously, exposed the mice to an inhalation challenge with corn dust extract (CDE), and measured inflammation and the development of airway hyperreactivity. Pretreatment with IL-10, in comparison to saline, reduced the concentration and percentage of polymorphonuclear cells in the lavage fluid 30 min after the inhalation challenge with CDE ( P < 0.05). In comparison to saline-treated mice, IL-10 did not significantly alter the degree of airway hyperreactivity 30 min after the exposure to CDE. IL-10-treated mice lavaged 18 h after challenge with CDE also exhibited a lower percentage of polymorphonuclear cells in the lavage fluid ( P < 0.05) and had significantly less airway hyperreactivity than did mice pretreated with the saline placebo ( P < 0.05). These findings indicate that exogenous IL-10 is effective in reducing airway inflammation and airway hyperreactivity due to the inhalation of CDE.
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Yamaya, Mutsuo, Hidekazu Nishimura, Kyoko Shinya, Yukimasa Hatachi, Takahiko Sasaki, Hiroyasu Yasuda, Motoki Yoshida et al. "Inhibitory effects of carbocisteine on type A seasonal influenza virus infection in human airway epithelial cells". American Journal of Physiology-Lung Cellular and Molecular Physiology 299, n.º 2 (agosto de 2010): L160—L168. http://dx.doi.org/10.1152/ajplung.00376.2009.
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Type A human seasonal influenza (FluA) virus infection causes exacerbations of bronchial asthma and chronic obstructive pulmonary disease (COPD). l-carbocisteine, a mucolytic agent, reduces the frequency of common colds and exacerbations in COPD. However, the inhibitory effects of l-carbocisteine on FluA virus infection are uncertain. We studied the effects of l-carbocisteine on FluA virus infection in airway epithelial cells. Human tracheal epithelial cells were pretreated with l-carbocisteine and infected with FluA virus (H3N2). Viral titers in supernatant fluids, RNA of FluA virus in the cells, and concentrations of proinflammatory cytokines in supernatant fluids, including IL-6, increased with time after infection. l-carbocisteine reduced viral titers in supernatant fluids, RNA of FluA virus in the cells, the susceptibility to FluA virus infection, and concentrations of cytokines induced by virus infection. The epithelial cells expressed sialic acid with an α2,6-linkage (SAα2,6Gal), a receptor for human influenza virus on the cells, and l-carbocisteine reduced the expression of SAα2,6Gal. l-carbocisteine reduced the number of acidic endosomes from which FluA viral RNA enters into the cytoplasm and reduced the fluorescence intensity from acidic endosomes. Furthermore, l-carbocisteine reduced NF-κB proteins including p50 and p65 in the nuclear extracts of the cells. These findings suggest that l-carbocisteine may inhibit FluA virus infection, partly through the reduced expression of the receptor for human influenza virus in the human airway epithelial cells via the inhibition of NF-κB and through increasing pH in endosomes. l-carbocisteine may reduce airway inflammation in influenza virus infection.
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Saunders, Ruth, Himanshu Kaul, Rachid Berair, Sherif Gonem, Amisha Singapuri, Amanda J. Sutcliffe, Latifa Chachi et al. "DP2 antagonism reduces airway smooth muscle mass in asthma by decreasing eosinophilia and myofibroblast recruitment". Science Translational Medicine 11, n.º 479 (13 de febrero de 2019): eaao6451. http://dx.doi.org/10.1126/scitranslmed.aao6451.
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Increased airway smooth muscle mass, a feature of airway remodeling in asthma, is the strongest predictor of airflow limitation and contributes to asthma-associated morbidity and mortality. No current drug therapy for asthma is known to affect airway smooth muscle mass. Although there is increasing evidence that prostaglandin D2 type 2 receptor (DP2) is expressed in airway structural and inflammatory cells, few studies have addressed the expression and function of DP2 in airway smooth muscle cells. We report that the DP2 antagonist fevipiprant reduced airway smooth muscle mass in bronchial biopsies from patients with asthma who had participated in a previous randomized placebo-controlled trial. We developed a computational model to capture airway remodeling. Our model predicted that a reduction in airway eosinophilia alone was insufficient to explain the clinically observed decrease in airway smooth muscle mass without a concomitant reduction in the recruitment of airway smooth muscle cells or their precursors to airway smooth muscle bundles that comprise the airway smooth muscle layer. We experimentally confirmed that airway smooth muscle migration could be inhibited in vitro using DP2-specific antagonists in an airway smooth muscle cell culture model. Our analyses suggest that fevipiprant, through antagonism of DP2, reduced airway smooth muscle mass in patients with asthma by decreasing airway eosinophilia in concert with reduced recruitment of myofibroblasts and fibrocytes to the airway smooth muscle bundle. Fevipiprant may thus represent a potential therapy to ameliorate airway remodeling in asthma.
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Ameredes, Bill T., Leo E. Otterbein, Lauryn K. Kohut, Amber L. Gligonic, William J. Calhoun y Augustine M. K. Choi. "Low-dose carbon monoxide reduces airway hyperresponsiveness in mice". American Journal of Physiology-Lung Cellular and Molecular Physiology 285, n.º 6 (diciembre de 2003): L1270—L1276. http://dx.doi.org/10.1152/ajplung.00145.2003.
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Carbon monoxide (CO) in expired gas has been shown to be elevated with asthma; however, its function is not known, and there is some potential that it may serve a bronchoprotective role to decrease airway hyperresponsiveness (AHR). Thus the ability of CO to reverse methacholine (MCh)-induced bronchoconstriction was evaluated in C57BL/6 (C57) and A/J mice with and without airway inflammation produced by ovalbumin (OVA). Acutely administered CO (1% in air, 10 min) reduced MCh-driven increases in lung resistance in OVA-challenged C57 mice by an average of 50% (from 14.5 to 7.1 cmH2O·ml-1·s-1), whereas no effect was observed in naïve C57 mice or OVA-challenged C57 mice inhaling air alone. Acutely inhaled CO (500 ppm = 0.05%, for 10 min) reduced MCh-induced airway reactivity (AR) by 20-60% in airway hyperresponsive naïve A/J mice, whereas repeated 10-min administrations of 500 ppm CO over a 5-day period decreased AR by 50%. Repeated administration of low-dose CO [250 (0.025%) and (0.05%) 500 ppm, 1 h/day, 5 days] to A/J mice with airway inflammation likewise resulted in a drop of AR by 50%, compared with those not receiving CO. Inhibition of guanylyl cyclase/guanosine 3′,5′-cyclic monophosphothioate (cGMP) using 1H-[1,2,4] oxydiazolo[4,3-a]quinoxalin-1-one or a competitive inhibitor, Rp diastereomers of 8-bromo-cGMP, resulted in inhibition of the effect of CO on AHR, suggesting that the effects of CO were mediated through this mechanism. These results indicate that low-dose CO can effectively reverse AHR in the presence and absence of airway inflammation in mice and suggest a potential role for CO in the modulation of AHR.
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Zhang, Wei, Zhi Gang Guo, Xiao Dong Wang, Liang Dong An y Hui Chen. "Research of Automotive Airbag Automatic Folding Device". Advanced Materials Research 658 (enero de 2013): 390–94. http://dx.doi.org/10.4028/www.scientific.net/amr.658.390.
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In order to improve the quality of folding and increase the production efficiency in the process of airbag folding，a new airbag automatic folding device（AAFD） with programmable logic controller(PLC) as control unit and magnetic induction sensors as well as photoelectric sensors as trace positional parameters of rolling bag institutions has been developed. In addition, the important data of the device can also be stored by structured query language (SQL) which can query, update, and manage relational database system. The experimental results showed that, compared to a traditional AFD, the uniformity of gap during the production of airbag folding had been significantly improved, and the impact of human interference had also been reduced. Meanwhile, the device can produce a variety of types of products and also can ensure the quality of products, improve the production efficiency, and enhance the degree of standardization of the device.
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Germain, Nöella, Elisabeth Boichot, Jean-Michel Planquois y Vincent Lagente. "Reduced Airway Hyperresponsiveness by Phosphodiesterase 3 and 4 Inhibitors in Guinea-Pigs". Mediators of Inflammation 8, n.º 3 (1999): 153–57. http://dx.doi.org/10.1080/09629359990487.
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The aim of the present study was to compare the effects of selective phosphodiesterase (PDE) 3, 4 and 5 inhibitors on antigen-induced airway hyperresponsiveness in sensitized guinea-pigs. When the sensitized guinea-pigs were orally pre-treated with the selective PDE4 inhibitor, Ro 20-1724 (30 mg/kg), and studied 48 h after OA, a significant reduction (p<0.01) of the leftward shift of the dose-response curve to ACh was noted, whereas it was ineffective at the lower dose (10 mg/kg). Administration of the selective PDE3 inhibitor, milrinone (30 mg/kg) also elicited a significant reduction (p<0.01) of the airway hyperresponsiveness, whereas the PDE5 inhibitor zaprinast (30 mg/kg) was ineffective. These results show that both PDE3 and PDE4 inhibitors are able to inhibit the antigen-induced airway hyperresponsiveness in sensitized guinea-pigs and support the potential utility of selective PDE inhibitors in the treatment of asthma.
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Wu, Qun, Richard J. Martin, John G. Rino, Samithamby Jeyaseelan, Rachel Breed y Hong Wei Chu. "A deficient TLR2 signaling promotes airway mucin production inMycoplasma pneumoniae-infected allergic mice". American Journal of Physiology-Lung Cellular and Molecular Physiology 292, n.º 5 (mayo de 2007): L1064—L1072. http://dx.doi.org/10.1152/ajplung.00301.2006.
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The original hygiene hypothesis suggests that early childhood respiratory infections preceding allergen exposure may decrease the prevalence of allergic diseases. We have recently demonstrated that Mycoplasma pneumoniae infection preceding allergen exposure reduced allergic responses in mice. However, the molecular mechanisms underlying the protective role of M. pneumoniae in allergic responses, particularly airway mucin production, remain unclear. Wild-type and Toll-like receptor 2 (TLR2)-deficient mice with a respiratory M. pneumoniae infection preceding allergen (ovalbumin) challenge were utilized to determine the regulatory role of TLR2-IFN-γ signaling pathway in airway mucin expression. Furthermore, air-liquid interface cultures of mouse primary tracheal epithelial cells were performed to examine the effects of IFN-γ on mucin expression. In wild-type mice, M. pneumoniae infection preceding allergen challenge significantly reduced airway mucins but increased IFN-γ. In sharp contrast, in TLR2-deficient mice, M. pneumoniae preceding allergen challenge resulted in increased mucin protein without a noticeable change of IFN-γ. In cultured mouse primary tracheal epithelial cells, IFN-γ was shown to directly inhibit mucin expression in a dose-dependent manner. Our study demonstrates for the first time that a respiratory M. pneumoniae infection preceding allergen challenge reduces airway epithelial mucin expression in part through TLR2-IFN-γ signaling pathway. A bacterial infection in asthmatic subjects with weakened TLR2-IFN-γ signaling may result in an exaggerated airway mucin production.
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Barnaby, Roxanna, Katja Koeppen y Bruce A. Stanton. "Cyclodextrins reduce the ability of Pseudomonas aeruginosa outer-membrane vesicles to reduce CFTR Cl− secretion". American Journal of Physiology-Lung Cellular and Molecular Physiology 316, n.º 1 (1 de enero de 2019): L206—L215. http://dx.doi.org/10.1152/ajplung.00316.2018.
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Pseudomonas aeruginosa secretes outer-membrane vesicles (OMVs) that fuse with cholesterol-rich lipid rafts in the apical membrane of airway epithelial cells and decrease wt-CFTR Cl− secretion. Herein, we tested the hypothesis that a reduction of the cholesterol content of CF human airway epithelial cells by cyclodextrins reduces the inhibitory effect of OMVs on VX-809 (lumacaftor)-stimulated Phe508del CFTR Cl− secretion. Primary CF bronchial epithelial cells and CFBE cells were treated with vehicle, hydroxypropyl-β-cyclodextrin (HPβCD), or methyl-β-cyclodextrin (MβCD), and the effects of OMVs secreted by P. aeruginosa on VX-809 stimulated Phe508del CFTR Cl− secretion were measured in Ussing chambers. Neither HPβCD nor MβCD were cytotoxic, and neither altered Phe508del CFTR Cl− secretion. Both cyclodextrins reduced OMV inhibition of VX-809-stimulated Phe508del-CFTR Cl− secretion when added to the apical side of CF monolayers. Both cyclodextrins also reduced the ability of P. aeruginosa to form biofilms and suppressed planktonic growth of P. aeruginosa. Our data suggest that HPβCD, which is in clinical trials for Niemann-Pick Type C disease, and MβCD, which has been approved by the U.S. Food and Drug Administration for use in solubilizing lipophilic drugs, may enhance the clinical efficacy of VX-809 in CF patients when added to the apical side of airway epithelial cells, and reduce planktonic growth and biofilm formation by P. aeruginosa. Both effects would be beneficial to CF patients.
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Greville, H. W., M. E. Arnup, S. N. Mink, L. Oppenheimer y N. R. Anthonisen. "Mechanism of reduced maximum expiratory flow in dogs with compensatory lung growth". Journal of Applied Physiology 60, n.º 2 (1 de febrero de 1986): 441–48. http://dx.doi.org/10.1152/jappl.1986.60.2.441.
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We examined the mechanism of the reduced maximum expiratory flow rates (Vmax) in a dog model of postpneumonectomy compensatory lung growth. During forced expiration, a Pitot-static tube was used to locate the airway site of flow limitation, or choke point, and to measure dynamic intrabronchial pressures. The factors determining Vmax were calculated and the results analyzed in terms of the wave-speed theory of flow limitation. Measurements were made at multiple lung volumes and during ventilation both with air and with HeO2. Five of the puppies had undergone a left pneumonectomy at 10 wk of age, and 5 littermate controls had undergone a sham operation. All dogs were studied at 26 wk of age, at which time compensatory lung growth had occurred in the postpneumonectomy group. Vmax was markedly decreased in the postpneumonectomy group compared with control, averaging 42% of the control flow rates from 58 to 35% of the vital capacity (VC). At 23% of the VC, Vmax was 15% less than control. Choke points were more peripheral in the postpneumonectomy dogs compared with controls at all volumes. The total airway pressure was the same at the choke-point airway in the postpneumonectomy dogs as that in the same airway in the control dogs, suggesting that the airways of the postpneumonectomy dogs displayed different bronchial area-pressure behavior from the control dogs. Despite the decreased Vmax on both air and HeO2, the density dependence of flow was high in the postpneumonectomy dogs and the same as controls at all lung volumes examined.
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Mabalirajan, Ulaganathan, Jyotirmoi Aich, Geeta Devi Leishangthem, Surendra Kumar Sharma, Amit Kumar Dinda y Balaram Ghosh. "Effects of vitamin E on mitochondrial dysfunction and asthma features in an experimental allergic murine model". Journal of Applied Physiology 107, n.º 4 (octubre de 2009): 1285–92. http://dx.doi.org/10.1152/japplphysiol.00459.2009.
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We showed recently that IL-4 causes mitochondrial dysfunction in allergic asthma. IL-4 is also known to induce 12/15-lipoxygenase (12/15-LOX), a potent candidate molecule in asthma. Because vitamin E (Vit-E) reduces IL-4 and inhibits 12/15-LOX in vitro, here we tested the hypothesis that Vit-E may be effective in restoring key mitochondrial dysfunctions, thus alleviating asthma features in an experimental allergic murine model. Ovalbumin (OVA)-sensitized and challenged male BALB/c mice showed the characteristic features of asthma such as airway hyperresponsiveness (AHR), airway inflammation, and airway remodeling. In addition, these mice showed increase in the expression and metabolites of 12/15-LOX, reduction in the activity and expression of the third subunit of mitochondrial cytochrome- c oxidase, and increased cytochrome c in lung cytosol, which indicate that OVA sensitization and challenge causes mitochondrial dysfunction. Vit-E was administered orally to these mice, and 12/15-LOX expression, key mitochondrial functions, ultrastructural changes of mitochondria in bronchial epithelia, and asthmatic parameters were determined. Vit-E treatment reduced AHR, Th2 response including IL-4, IL-5, IL-13, and OVA-specific IgE, eotaxin, transforming growth factor-β1, airway inflammation, expression and metabolites of 12/15-LOX in lung cytosol, lipid peroxidation, and nitric oxide metabolites in the lung, restored the activity and expression of the third subunit of cytochrome- c oxidase in lung mitochondria and bronchial epithelia, respectively, reduced the appearance of cytochrome c in lung cytosol, and also restored mitochondrial ultrastructural changes of bronchial epithelia. In summary, these findings show that Vit-E reduces key mitochondrial dysfunctions and alleviates asthmatic features.
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Xue, Z., L. Zhang, R. Ramchandani, Y. Liu, V. B. Antony, S. J. Gunst y R. S. Tepper. "Respiratory system responsiveness in rabbits in vivo is reduced by prolonged continuous positive airway pressure". Journal of Applied Physiology 99, n.º 2 (agosto de 2005): 677–82. http://dx.doi.org/10.1152/japplphysiol.00165.2005.
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Active, nonanesthetized, tracheotomized rabbits were subjected to continuous positive airway pressure (CPAP) for 4 days to determine the effects of chronic mechanical strain on lung and airway function. Rabbits were maintained for 4 days at a CPAP of 6 cmH2O (high CPAP), at a CPAP of 0 cmH2O (low CPAP), or without tracheostomy (no CPAP). After treatment with CPAP, changes in respiratory resistance in response to increasing concentrations of inhaled ACh were measured during mechanical ventilation to evaluate respiratory system responsiveness in vivo. Intraparenchymal bronchial segments were isolated from the lungs of all animals to evaluate airway smooth muscle responsiveness and bronchial compliance in vitro. Rabbits maintained for 4 days at high CPAP demonstrated significantly lower responsiveness to ACh compared with rabbits that were maintained at low CPAP or with no CPAP. Airways isolated from the lungs of animals subjected to the chronic application of high CPAP were also less responsive to ACh in vitro than the airways isolated from animals subjected to low CPAP or no CPAP. The persistence of the decreased responsiveness in the excised airway tissues suggests that the decreased respiratory system responsiveness observed in vivo results primarily from direct effects on the airways. The results demonstrate that the application of prolonged mechanical strain in vivo can reduce airway reactivity.
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Doran, Emma, David F. Choy, Aarti Shikotra, Claire A. Butler, Declan M. O'Rourke, James A. Johnston, Adrien Kissenpfennig, Peter Bradding, Joseph R. Arron y Liam G. Heaney. "Reduced epithelial suppressor of cytokine signalling 1 in severe eosinophilic asthma". European Respiratory Journal 48, n.º 3 (23 de junio de 2016): 715–25. http://dx.doi.org/10.1183/13993003.00400-2015.
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Severe asthma represents a major unmet clinical need. Eosinophilic inflammation persists in the airways of many patients with uncontrolled asthma, despite high-dose inhaled corticosteroid therapy. Suppressors of cytokine signalling (SOCS) are a family of molecules involved in the regulation of cytokine signalling via inhibition of the Janus kinase–signal transducers and activators of transcription pathway. We examined SOCS expression in the airways of asthma patients and investigated whether this is associated with persistent eosinophilia.Healthy controls, mild/moderate asthmatics and severe asthmatics were studied. Whole genome expression profiling, quantitative PCR and immunohistochemical analysis were used to examine expression of SOCS1, SOCS2 and SOCS3 in bronchial biopsies. Bronchial epithelial cells were utilised to examine the role of SOCS1 in regulating interleukin (IL)-13 signalling in vitro.SOCS1 gene expression was significantly lower in the airways of severe asthmatics compared with mild/moderate asthmatics, and was inversely associated with airway eosinophilia and other measures of T-helper type 2 (Th2) inflammation. Immunohistochemistry demonstrated SOCS1 was predominantly localised to the bronchial epithelium. SOCS1 overexpression inhibited IL-13-mediated chemokine ligand (CCL) 26 (eotaxin-3) mRNA expression in bronchial epithelial cells.Severe asthma patients with persistent airway eosinophilia and Th2 inflammation have reduced airway epithelial SOCS1 expression. SOCS1 inhibits epithelial IL-13 signalling, supporting its key role in regulating Th2-driven eosinophilia in severe asthma.
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Mikami, Maya, Gene T. Yocum, Nicola M. Heller y Charles W. Emala. "Reduced allergic lung inflammation and airway responsiveness in mice lacking the cytoskeletal protein gelsolin". American Journal of Physiology-Lung Cellular and Molecular Physiology 319, n.º 5 (1 de noviembre de 2020): L833—L842. http://dx.doi.org/10.1152/ajplung.00065.2020.
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Airway smooth muscle hyperresponsiveness associated with chronic airway inflammation leads to the typical symptoms of asthma including bronchoconstriction and wheezing. Asthma severity is associated with airway inflammation; therefore, reducing airway inflammation is an important therapeutic target. Gelsolin is an actin capping and severing protein that has been reported to be involved in modulation of the inflammatory response. Using mice genetically lacking gelsolin, we evaluated the role of gelsolin in the establishment of house dust mite (HDM) antigen-induced allergic lung inflammation. The genetic absence of gelsolin was found to be protective against HDM sensitization, resulting in reduced lung inflammation, inflammatory cytokines, and Muc5AC protein in bronchoalveolar lavage (BAL) fluid. The number of eosinophils, lymphocytes, and interstitial macrophages in the BAL were increased after HDM sensitization in wild-type mice but were attenuated in gelsolin-null mice. The observed attenuation of inflammation may be partly due to delayed migration of immune cells, because the reduced eosinophils in the BALs from gelsolin-null mice compared with controls occurred despite similar amounts of the chemoattractant eotaxin. Splenic T cells demonstrated similar proliferation rates, but ex vivo alveolar macrophage migration was delayed in gelsolin-null mice. In vivo, the reduced lung inflammation after HDM sensitization in gelsolin-null mice was associated with significantly diminished airway resistance to inhaled methacholine compared with HDM-treated wild-type mice. Our results suggest that modulation of gelsolin expression or function in selective inflammatory cell types that modulate allergic lung inflammation could be a therapeutic approach for asthma.
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Akay, Metin, J. C. Leiter y J. Andrew Daubenspeck. "Reduced respiratory-related evoked activity in subjects with obstructive sleep apnea syndrome". Journal of Applied Physiology 94, n.º 2 (1 de febrero de 2003): 429–38. http://dx.doi.org/10.1152/japplphysiol.00018.2001.
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Midlatency respiratory-related evoked potentials were measured during wakefulness by using a 60-electrode array placed over the cortical region of the scalp. We studied the responses evoked by 200-ms pressure pulses at −5 and −10 cmH2O applied at inspiratory onset and during control tests (no pressure applied) in 14 subjects with obstructive sleep apnea syndrome (OSAS) and 18 normal subjects. Wavelet decomposition was used to smooth and dissect the respiratory-related evoked potentials in frequency and time in 8 frequency bands. After denoising, selected wavelet scales were used to reconstruct the respiratory-related evoked potentials, which were quantified by using global field power estimates. The time course of the global field power activity in OSAS subjects compared with normal subjects was significantly depressed in the period 55–70 ms poststimulus onset, a time when afferent traffic from upper airway receptors arrives in normal subjects. The reduced evoked response in subjects with OSAS suggests that these subjects receive less afferent input from upper airway mechanoreceptors. This may reflect reduced sensitivity of mechanoreceptors or reduced mechanoreceptor stimulation due to decreased upper airway compliance during wakefulness in OSAS.
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Cortjens, Bart, Rineke de Jong, Judith G. Bonsing, Job B. M. van Woensel, Adriaan F. G. Antonis y Reinout A. Bem. "Local dornase alfa treatment reduces NETs-induced airway obstruction during severe RSV infection". Thorax 73, n.º 6 (5 de agosto de 2017): 578–80. http://dx.doi.org/10.1136/thoraxjnl-2017-210289.
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Respiratory syncytial virus (RSV) infection is characterised by airway obstruction with mucus plugs, containing DNA networks in the form of neutrophil extracellular traps (NETs). We investigated the effect of dornase alfa on histopathological NETs-induced airway obstruction and viral load in an age-relevant calf model of severe bovine RSV disease. As compared with the control animals, dornase alfa treatment resulted in a strong reduction of NETs-induced airway obstruction. Viral load in the lower respiratory tract was not different between the two groups. We conclude that NETs form a relevant target for treatment of airway obstruction in severe RSV disease.
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Haczku, Angela, Elena N. Atochina, Yaniv Tomer, Yang Cao, Colleen Campbell, Seth T. Scanlon, Scott J. Russo, Goran Enhorning y Michael F. Beers. "The late asthmatic response is linked with increased surface tension and reduced surfactant protein B in mice". American Journal of Physiology-Lung Cellular and Molecular Physiology 283, n.º 4 (1 de octubre de 2002): L755—L765. http://dx.doi.org/10.1152/ajplung.00062.2002.
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Pulmonary surfactant dysfunction may significantly contribute to small airway obstruction during the asthmatic response, but neither its exact role nor its regulation is clear. Surfactant function and composition was studied in an Aspergillus fumigatus ( Af)-induced late-phase allergic airway response in sensitized BALB/c mice. The peak of Af-induced airway hyperresponsiveness in sensitized and challenged mice 24 h after allergen provocation coincided with a significant fall in surface activity of the pulmonary surfactant. The underlying changes included time-dependent elaboration of eotaxin and IL-5 followed by eosinophil influx into the airways. The height of airway inflammation and hyperresponsiveness was preceded by release of IL-4 and marked reductions in surfactant protein (SP)-B, a hydrophobic surfactant protein responsible for maintaining low surface tension of the lining fluid of distal air spaces. Furthermore, intratracheal administration of IL-4 significantly inhibited SP-B, indicating a regulatory role of this cytokine in the surfactant biophysical changes. Thus surfactant dysfunction induced by an IL-4-driven SP-B deficiency after allergen provocation may be an important part of the late asthmatic airway response.
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Murlas, Christopher. "Effects of mucosal removal on guinea-pig airway smooth muscle responsiveness". Clinical Science 70, n.º 6 (1 de junio de 1986): 571–75. http://dx.doi.org/10.1042/cs0700571.
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1. The contractile response to histamine, acetylcholine (ACh), KCl or electrical field stimulation (EFS) was examined in paired tracheal rings (one of each being denuded by mucosal rubbing), which were mounted in muscle chambers filled with a continuously aerated physiological salt solution at 37°C. 2. Removal of the respiratory mucosa increased the sensitivity of airway muscle to ACh, histamine and EFS, but not to KCl. The hypersensitivity of denuded rings to histamine and EFS was greater than to ACh. Atropine reduced the histamine hypersensitivity observed. 3. Pretreating intact preparations with indomethacin augmented their responsiveness to EFS, histamine and ACh. 4. Indomethacin augmentation of histamine- and EFS-induced responses was greater in preparations without epithelium. 5. We conclude that the airway mucosa may be associated with a factor that reduces airway smooth muscle responsiveness to stimulation.
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Ray, Andrew D., Ulysses J. Magalang, Charles P. Michlin, Toshiyuki Ogasa, John A. Krasney, Luc E. Gosselin y Gaspar A. Farkas. "Intermittent hypoxia reduces upper airway stability in lean but not obese Zucker rats". American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 293, n.º 1 (julio de 2007): R372—R378. http://dx.doi.org/10.1152/ajpregu.00038.2007.
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Obstructive sleep apnea involves intermittent periods of airway occlusions that lead to repetitive oxygen desaturations. Exposure to chronic intermittent hypoxia (IH) in rats increases diurnal blood pressure and alters skeletal muscle physiology. The impact of IH on upper airway muscle function is unknown. We hypothesize that IH exposure increases upper airway collapsibility in rats due to alterations of the muscles surrounding the upper airway. Lean and obese rats were exposed to cyclic alterations in O2 levels (20.6%-5%) every 90 s, 8 h/day for 6 days/wk for 12 wk. Following the exposure period, arterial pressure was recorded via the tail artery in conscious unrestrained rats. Mean arterial pressure was increased in lean IH but not in obese IH-exposed Zucker rats ( P < 0.05). The pharyngeal pressure associated with airway collapse (Pcrit) was measured under anesthesia during baseline conditions and then during supramaximal stimulation of the hypoglossal nerve (cnXII). Baseline Pcrit was more positive (more collapsible) in lean but not obese rats following 12 wk of IH ( P < 0.05), while supramaximal stimulation of cnXII increased airway stability (decreased Pcrit) in both lean and obese Zucker rats following IH to levels that were similar to their respective room air controls. The in vitro peak tension and the expression of the individual myosin heavy chain isoforms from the upper airway muscles were unaltered following IH. We conclude that IH leads to increases in baseline collapsibility in lean Zucker rats exposed to IH by nonmyogenic mechanisms.
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Haas, F., N. Levin, S. Pasierski, M. Bishop y K. Axen. "Reduced hyperpnea-induced bronchospasm following repeated cold air challenge". Journal of Applied Physiology 61, n.º 1 (1 de julio de 1986): 210–14. http://dx.doi.org/10.1152/jappl.1986.61.1.210.
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This study assessed reduction in expiratory function in 12 asthmatic subjects both after 5 min of cold air provocation (CAP) with dry air conditioned to approximately 0 degrees C and after exercise (to 85% of predicted maximum heart rate) while breathing ambient room air (approximately 21 degrees C and 40% relative humidity). These assessments were done both before and after the following training protocol. Three 5-min periods of isocapnic cold air hyperpnea separated by 5-min rest periods were performed breathing 0 degrees to -10 degrees C air, for 36 sessions over 12 wk. As expected, pretraining expiratory function was significantly reduced (P less than 0.001) after both CAP and exercise. The posttraining reduction in expiratory function after CAP and exercise, however, was significantly less pronounced (largest P less than 0.05). These data support our hypothesis that repeated bouts of cold air challenge result in airway acclimatization to cold air and consequent decrease in exercise-induced bronchospasm. Acclimatization may result directly either by habituation of the airways or by vasodilation leading to increased bronchial blood flow and consequent reduced airway cooling. An unanticipated finding, though, is that repeated cold air challenge may also cause long-term inflammatory changes in the airways. A significant percentage of subjects experienced reduced base-line pulmonary function and overall exacerbation of asthma symptoms during the training period.
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Sussan, Thomas E., Sachin Gajghate, Samit Chatterjee, Pooja Mandke, Sarah McCormick, Kuladeep Sudini, Sarvesh Kumar et al. "Nrf2 reduces allergic asthma in mice through enhanced airway epithelial cytoprotective function". American Journal of Physiology-Lung Cellular and Molecular Physiology 309, n.º 1 (1 de julio de 2015): L27—L36. http://dx.doi.org/10.1152/ajplung.00398.2014.
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Asthma development and pathogenesis are influenced by the interactions of airway epithelial cells and innate and adaptive immune cells in response to allergens. Oxidative stress is an important mediator of asthmatic phenotypes in these cell types. Nuclear erythroid 2-related factor 2 ( Nrf2) is a redox-sensitive transcription factor that is the key regulator of the response to oxidative and environmental stress. We previously demonstrated that Nrf2-deficient mice have heightened susceptibility to asthma, including elevated oxidative stress, inflammation, mucus, and airway hyperresponsiveness (AHR) (Rangasamy T, Guo J, Mitzner WA, Roman J, Singh A, Fryer AD, Yamamoto M, Kensler TW, Tuder RM, Georas SN, Biswal S. J Exp Med 202: 47–59, 2005). Here we dissected the role of Nrf2 in lung epithelial cells and tested whether genetic or pharmacological activation of Nrf2 reduces allergic asthma in mice. Cell-specific activation of Nrf2 in club cells of the airway epithelium significantly reduced allergen-induced AHR, inflammation, mucus, Th2 cytokine secretion, oxidative stress, and airway leakiness and increased airway levels of tight junction proteins zonula occludens-1 and E-cadherin. In isolated airway epithelial cells, Nrf2 enhanced epithelial barrier function and increased localization of zonula occludens-1 to the cell surface. Pharmacological activation of Nrf2 by 2-trifluoromethyl-2′-methoxychalone during the allergen challenge was sufficient to reduce allergic inflammation and AHR. New therapeutic options are needed for asthma, and this study demonstrates that activation of Nrf2 in lung epithelial cells is a novel potential therapeutic target to reduce asthma susceptibility.
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Wagenaar, Gerry T. M., Pieter S. Hiemstra y Reinoud Gosens. "Therapeutic potential of soluble guanylate cyclase modulators in neonatal chronic lung disease". American Journal of Physiology-Lung Cellular and Molecular Physiology 309, n.º 10 (15 de noviembre de 2015): L1037—L1040. http://dx.doi.org/10.1152/ajplung.00333.2015.
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Supplemental oxygen after premature birth results in aberrant airway, alveolar, and pulmonary vascular development with an increased risk for bronchopulmonary dysplasia, and development of wheeze and asthma, pulmonary hypertension, and chronic obstructive pulmonary disease in survivors. Although stimulation of the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cGMP signal transduction pathway has significant beneficial effects on disease development in animal models, so far this could not be translated to the clinic. Oxidative stress reduces the NO-sGC-cGMP pathway by oxidizing heme-bound sGC, resulting in inactivation or degradation of sGC. Reduced sGC activity and/or expression is associated with pathology due to premature birth, oxidative stress-induced lung injury, including impaired alveolar maturation, smooth muscle cell (SMC) proliferation and contraction, impaired airway relaxation and vasodilation, inflammation, pulmonary hypertension, right ventricular hypertrophy, and an aggravated response toward hyperoxia-induced neonatal lung injury. Recently, Britt et al. (10) demonstrated that histamine-induced Ca2+ responses were significantly elevated in hyperoxia-exposed fetal human airway SMCs compared with normoxic controls and that this hyperoxia-induced increase in the response was strongly reduced by NO-independent stimulation and activation of sGC. These recent studies highlight the therapeutic potential of sGC modulators in the treatment of preterm infants for respiratory distress with supplemental oxygen. Such treatment is aimed at improving aberrant alveolar and vascular development of the neonatal lung and preventing the development of wheezing and asthma in survivors of premature birth. In addition, these studies highlight the suitability of fetal human airway SMCs as a translational model for pathological airway changes in the neonate.
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Minamoto, Kanji y David J. Pinsky. "Recipient iNOS but Not eNOS Deficiency Reduces Luminal Narrowing in Tracheal Allografts". Journal of Experimental Medicine 196, n.º 10 (18 de noviembre de 2002): 1321–33. http://dx.doi.org/10.1084/jem.20012135.
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Chronic airway rejection is characterized by prolonged inflammation, epithelial damage, and eventual luminal obliterative bronchiolitis (OB). In cardiac allografts, the inducible nitric oxide synthase (iNOS) promotes acute rejection but paradoxically reduces neointimal formation, the hallmark of chronic rejection. The specific roles of NOS isoforms in modulating lymphocyte traffic and airway rejection are not known. Using a double lumen mouse tracheal transplant model, tracheal grafts from B10.A (allo) or C57BL/6J (iso) mice were transplanted into cyclosporine-treated wild-type (WT) iNOS−/− or endothelial NOS (eNOS)−/− recipients. OB was observed in WT tracheal allografts at 3 weeks (53 ± 2% luminal occlusion vs. 17 ± 1% for isografts, P < 0.05) with sites of obstructive lesion formation coinciding with areas of CD3+ CD8+ T cell–rich lymphocytic bronchitis. In contrast, allografts in iNOS−/− recipients exhibited reductions in local expression of proinflammatory chemokines and cytokines, graft T cell recruitment and apoptosis, and luminal obliteration (29 ± 2%, P < 0.05 vs. WT allografts). Recipient eNOS deficiency, however, suppressed neither chemokine expression, lymphocyte infiltration, nor airway occlusion (54 ± 2%). These data demonstrate that iNOS exacerbates luminal obliteration of airway allografts in contrast with the known suppression by iNOS of cardiac allograft vasculopathy. Because iNOS−/− airways transplanted into WT allograft hosts are not protected from rejection, these data suggest that iNOS expressed by graft-infiltrating leukocytes exerts the dominant influence on airway rejection.
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Lukacs, Nicholas W., M. Michael Glovsky y Peter A. Ward. "Complement-dependent immune complex-induced bronchial inflammation and hyperreactivity". American Journal of Physiology-Lung Cellular and Molecular Physiology 280, n.º 3 (1 de marzo de 2001): L512—L518. http://dx.doi.org/10.1152/ajplung.2001.280.3.l512.
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Bronchoconstriction responses in the airway are caused by multiple insults and are the hallmark symptom in asthma. In an acute lung injury model in mice, IgG immune complex deposition elicited severe airway hyperreactivity that peaked by 1 h, was maintained at 4 h, and was resolved by 24 h. The depletion of complement with cobra venom factor (CVF) markedly reduced the hyperreactive airway responses, suggesting that complement played an important role in the response. Blockade of C5a with specific antisera also significantly reduced airway hyperreactivity in this acute lung model. Complement depletion by CVF treatment significantly reduced tumor necrosis factor and histamine levels in bronchoalveolar lavage fluids, correlating with reductions in airway hyperreactivity. To further examine the role of specific complement requirement, we initiated the immune complex response in C5-sufficient and C5-deficient congenic animals. The airway hyperreactivity response was partially reduced in the C5-deficient mice. Complement depletion with CVF attenuated airway hyperreactivity in the C5-sufficient mice but had a lesser effect on the airway hyperreactive response and histamine release in bronchoalveolar lavage fluids in C5-deficient mice. These data indicate that acute lung injury in mice after deposition of IgG immune complexes induced airway hyperreactivity that is C5 and C5a dependent.
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Halayko, Andrew J., Edward Rector y Newman L. Stephens. "Airway smooth muscle cell proliferation: characterization of subpopulations by sensitivity to heparin inhibition". American Journal of Physiology-Lung Cellular and Molecular Physiology 274, n.º 1 (1 de enero de 1998): L17—L25. http://dx.doi.org/10.1152/ajplung.1998.274.1.l17.
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Growth and maturation state of airway smooth muscle cells (SMCs) are determinants of asthma pathophysiology. Heparin reduces airway SMC proliferation and arterial SMC replication and phenotypic modulation. Distinct arterial SMC subtypes, differing in heparin sensitivity, have been characterized. We assessed the cellular mechanisms underlying the growth and phenotype of heparin-treated canine tracheal myocytes in primary culture. Heparin reduced replication by 40%. Immunoblot assay of myosin, actin, and myosin light chain kinase revealed heparin had no effect on rapid spontaneous phenotypic modulation after the cells were plated. Heparin increased cellular protein and vimentin contents in confluent cultures, suggesting that it may induce hypertrophic growth. Cell cycle analysis revealed that heparin decreased serum-stimulated replicating myocyte number by 40%. Also, G2-M transit was 20% slower for the set of SMCs that proceeded past G1 in the presence of heparin. These data indicate that heparin does not inhibit airway SMC replication by blocking modulation from the contractile state. Moreover, airway smooth muscle is composed of distinct SMC populations differing in mitogen and antiproliferative mediator responsiveness. Identification of functionally divergent subgroups suggests that distinct sets of SMCs may contribute differentially to airway physiology and pathophysiology.
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Xue, Z., L. Zhang, Y. Liu, S. J. Gunst y R. S. Tepper. "Chronic inflation of ferret lungs with CPAP reduces airway smooth muscle contractility in vivo and in vitro". Journal of Applied Physiology 104, n.º 3 (marzo de 2008): 610–15. http://dx.doi.org/10.1152/japplphysiol.00241.2007.
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The mechanical stress imposed on the lungs during breathing is an important modulator of airway responsiveness in vivo. Our recent study demonstrated that continuous positive airway pressure applied to the lungs of nonanesthetized, tracheotomized rabbits for 4 days decreased lower respiratory system responsiveness to challenge with ACh (Xue Z, Zhang L, Ramchandani R, Liu Y, Antony VB, Gunst SJ, Tepper RS. J. Appl Physiol 99: 677–682, 2005). In addition, airway segments excised from the lungs of these animals and studied in vitro exhibited reduced contractility. However, the mechanism for this reduction in contractility was not determined. The stress-induced decrease in airway responsiveness could have resulted from alterations in the excitation-contraction coupling mechanisms of the smooth muscle cells, or it might reflect changes in the structure and/or composition of the airway wall tissues. In the present study, we assessed the effect of prolonged chronic stress of the lungs in vivo on airway smooth muscle force generation, myosin light chain phosphorylation, and airway wall structure. To enhance the potential development of stress-induced structural changes, we applied mechanical stress for a prolonged period of time of 2–3 wk. Our results demonstrate a direct connection between the decreased airway responsiveness caused by chronic mechanical stress of the lungs in vivo and a persistent decrease in contractile protein activation in the airway smooth muscle isolated from those lungs. The chronic stress also caused an increase in airway size but no detectable changes in the composition of the airway wall.
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Lokwani, Ravi, Peter A. B. Wark, Katherine J. Baines, Daniel Barker y Jodie L. Simpson. "Hypersegmented airway neutrophils and its association with reduced lung function in adults with obstructive airway disease: an exploratory study". BMJ Open 9, n.º 1 (enero de 2019): e024330. http://dx.doi.org/10.1136/bmjopen-2018-024330.
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ObjectivesThe significance of neutrophilic inflammation in obstructive airway disease remains controversial. Recent studies have demonstrated presence of an active neutrophil population in systemic circulation, featuring hypersegmented morphology, with high oxidative burst and functional plasticity in inflammatory conditions. The aim of this study was to characterise neutrophil subsets in bronchial lavage (BL) of obstructive airway disease participants (asthma, chronic obstructive pulmonary disease (COPD) and bronchiectasis) and healthy controls on the basis of nuclear morphology and to assess the association between neutrophil subsets and the clinical parameters of the obstructive airway disease participants.DesignA cross-sectional exploratory study.SettingJohn Hunter Hospital and Hunter Medical Research Institute, Australia.ParticipantsSeventy-eight adults with obstructive airway disease comprised those with stable asthma (n=39), COPD (n=20) and bronchiectasis (n=19) and 20 healthy controls.Materials and methodsCytospins were prepared and neutrophil subsets were classified based on nuclear morphology into hypersegmented (>4 lobes), normal (2–4 lobes) and banded (1 lobe) neutrophils and enumerated.ResultsNeutrophils from each subset were identified in all participants. Numbers of hypersegmented neutrophils were elevated in participants with airway disease compared with healthy controls (p<0.001). Both the number and the proportion of hypersegmented neutrophils were highest in COPD participants (median (Q1–Q3) of 1073.6 (258.8–2742) × 102/mL and 24.5 (14.0–46.5)%, respectively). An increased proportion of hypersegmented neutrophils in airway disease participants was significantly associated with lower forced expiratory volume in 1 s/forced vital capacity per cent (Spearman’s r=−0.322, p=0.004).ConclusionNeutrophil heterogeneity is common in BL and is associated with more severe airflow obstruction in adults with airway disease. Further work is required to elucidate the functional consequences of hypersegmented neutrophils in the pathogenesis of disease.